The objective of this application is to provide funds to renew the Washington University School of Medicine Drug Abuse Research Center. The center is a multidisciplinary one and consists of a Core Support budget and eight individual research elements which address several key biomedical and psychosocial issues in substance abuse. The biomedically related projects have as their focus the effects of narcotics on the endocrine-hypothalamus. Project 1 examines the effects of opiates on the hypothalamic-pituitary-gonadal axis in the male and probable role of endogeneous opioids in this axis; Project 2 is concerned with the neuroanatomical organization of the hypothalamus, particularly with respect to its neuroendocrine function; Project 3 explores the neurochemical mechanisms underlying the effects of narcotics and excitotoxic amino acids on luteinizing hormone release pathways; Project 4 focuses on attempts to utilize excitotoxic amino acids to selectively lesion endogeneous opioid-containing pathways in the hypothalamus; and, Project 5 will examine the influence of morphine and diazepam on the neurotoxicity produced by the excitotoxic amino acid, kainic acid. The psychosocial projects (6, 7 and 8) consist of a followup study of women admitted to this hospital 10 years ago with a diagnosis of alcoholism, drug abuse or depression (Project 6) and two projects in which female drug abusers (Project 7) and their children (Project 8) will be studied. Our Center is thus a multidisciplinary one with contributions from both our clinical (psychiatry and pediatrics) and pre-clinical (anatomy and neurobiology) Departments. As a final goal of our Research Center, we hope to provide an environment conducive for the training of post-doctoral fellows and the initiation of established investigators into the substance abuse field. Hence, the Washington University School of Medicine Drug Abuse Research Center is both a training and active research Center.